Partial protection against P. vivax infection diminishes hypnozoite burden and blood-stage relapses

Cell Host Microbe. 2021 May 12;29(5):752-756.e4. doi: 10.1016/j.chom.2021.03.011. Epub 2021 Apr 14.


Latent forms of Plasmodium vivax, called hypnozoites, cause malaria relapses from the liver into the bloodstream and are a major obstacle to malaria eradication. To experimentally assess the impact of a partially protective pre-erythrocytic vaccine on reducing Plasmodium vivax relapses, we developed a liver-humanized mouse model that allows monitoring of relapses directly in the blood. We passively infused these mice with a suboptimal dose of an antibody that targets the circumsporozoite protein prior to challenge with P. vivax sporozoites. Although this regimen did not completely prevent primary infection, antibody-treated mice experienced 62% fewer relapses. The data constitute unprecedented direct experimental evidence that suboptimal efficacy of infection-blocking antibodies, while not completely preventing primary infection, has a pronounced benefit in reducing the number of relapses. These findings suggest that a partially efficacious pre-erythrocytic Plasmodium vivax vaccine can have a disproportionately high impact in positive public health outcomes.

Keywords: Plasmodium vivax; circumsporozoite protein; humanized mouse; liver chimeric mouse; pre-erythrocytic vaccine; relapsing malaria.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood / parasitology*
  • Disease Models, Animal
  • Female
  • Humans
  • Liver / parasitology
  • Malaria, Vivax / blood
  • Malaria, Vivax / parasitology*
  • Mice
  • Plasmodium vivax / genetics
  • Plasmodium vivax / growth & development*
  • Recurrence